Abstract:

Objective  To observe the effects of MK801 and SB203580 on N-methyl-D-aspartic acid (NMDA)-induced cerebral cortical neurons injury and to explore the role of p38 mitogen-activated protein kinases(p38MAPK) signaling pathway in neurons injury and its possible mechanisms. Methods  Newborn SD rat cortical neurons were cultured for 7 days, then randomly divided into the control group, NMDA injury group, MK801 intervention group, SB203580 intervention group and combined intervention group（SB203580 + MK801）． MTT assays and LDH release were employed to assess viability of primary neurons and cell membrane damage, respectively. Acridine orange/ethidium bromide (AO/EB) double fluorescent staining was used to observe morphology and cell apoptosis. Expression of p38MAPK, BCL-2 and BAX were observed respectively by Western blotting. Results  Compared to the control group, NMDA injury group showed decreased cells viability(P＜0.01) and the expression of BCL-2(P＜0.05), increased leakage of LDH, the number of apoptotic cells and expression of p38MAPK and BAX(all P＜0.01). Compared to NMDA injury group, MK801 and SB203580 improved the cell viability, reduced LDH release rate and apoptosis, decreased the expressions of p38MAPK and BAX, and increased the expression of BCL-2(all P＜0.01). Conclusion  MK801 and SB203580 have protective effects on NMDA-induced injury neurons, and MK801 may protect the neurons from NMDA injury through p38MAPK pathway; they can inhibit the apoptosis-related proteins which are mediated by p38MAPK signaling pathway.

Key words: P38 mitogen-activated protein kinases; N-methyl-D-aspartic acid; N-methyl-D-aspartate receptors; Neuronal injury; Apoptosis